This revised Mentored Career Development application outlines a program of career development and research to study the relationship between hypothalamic-pituitary-adrenal (HPA) axis activity and hippocampal status in acute and chronic stress. Research subjects will consist of parents of children recently diagnosed with cancer. This population is unique because some will develop posttraumatic stress disorder (PTSD) and some will not, but all will undergo chronic stress during the year that they are followed as their child undergoes active cancer treatment Thus, it will be possible to study HPA-axis activity and hippocampal size and morphology in relation to PTSD status and chronic stress over time. I already have a theoretical and applied background in learning, behavior and anxiety. The career development and research plans are designed to enable me to develop proficiency and expertise in the use, analysis and application of neuroendocrinology to measure human stress responses and neuroimaging to address mechanisms of these responses. I will develop and test a theoretical model that examines the interaction between early structural and neuroendocrme abnormalities and subsequent traumatic experiences in a longitudinal design. Mentors include 1) a professor of neurology and director of a neuroimaging center; 2) a psychoneuroendocrinologist with special expertise in the psychobiology of stress and 3) a psychiatrist who is expert in medical trauma anxiety Relevant coursework and laboratory rotations from the curriculum of the Neuroscience Ph.D. program will be completed and mentors will direct in vivo training. Little is known about the time course of human HPA-axis dysregulation associated with exposure to extreme stress. Although previous studies have shown lower cortisol and hippocampal volume reductions in individuals with chronic PTSD, none have assessed HPA status and brain morphology concurrently. In addition, studies have been limited by single assessments often conducted years after the precipitating traumatic event. This proposal aims to investigate immediate and long-term HPA-axis activity and its relation to hippocampal size and morphology in recent-onset trauma. Cancer parents (both genders) with and without PTSD will be assessed within 1 month of the cancer diagnosis, then 12 months post-diagnosis for a) PTSD, depression, and other disorders); b) abnormal neuroendocrine activity (24-hour urinary cortisol) and c) abnormal hippocampal size and morphology (via Magnetic Resonance Imaging). The study will provide much-needed longitudinal data on HPA-axis and hippocampal abnormalities in acute and chronic stress.
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